Understanding of the signaling mechanisms by which pattern recognition receptors (PRRs) sense microbial infections and cellular stress engage innate immune responses is moving at an unprecedented rate. Developments in the past few years shed new light on how NOD-like receptors and inflammasomes are activated to promote cytokine production and cell death responses in the context of autoimmunity and microbial infection. Other findings clarified how extracellular and intracellular receptors of the Toll-like receptor, PYHIN/IFI, and helicase families respond to infections. In addition, intricate communication between PRRs and microbial commensals has emerged as a critical mechanism controlling immunity, and several fine-tuning mechanisms modulating PRR-induced immune responses have been discovered. Finally, a wealth of clinical information supporting the key roles of PRRs not only in host-microbe interactions, but also chronic autoinflammatory and autoimmune diseases in patients has emerged. This has spurred important translational medicine efforts to bring new therapies and diagnostics to the clinic. This conference unites an international group of academic and industry immunologists and microbiologists who study basic mechanisms of PRR signaling and their interaction with microbes in inflammatory disease models with clinicians and geneticists addressing the etiology of autoinflammatory and autoimmune diseases in patients. Gathering experts from these disparate research communities offers a unique opportunity to discuss new concepts of innate immune signaling and formulate novel approaches for modulating pathological mechanisms in human inflammatory diseases.